Department of Urology, Beijing Tian Tan Hospital, Capital Medical University, Beijing, China.
Department of Urology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, China.
J Immunol Res. 2021 Dec 16;2021:7753553. doi: 10.1155/2021/7753553. eCollection 2021.
Gasdermin B (GSDMB) is part of the gasdermin (GSDM) family, and they use varying means of domain interactions in molecules to adjust their pore-forming and lipid-binding actions. The GSDM family has roles in the regulation of cell differentiation and proliferation, particularly in the process of pyroptosis. Nonetheless, the correlation of GSDMB with immune infiltrates and its prognostic values in clear cell renal cell carcinoma (ccRCC) are still undefined. Therefore, we assessed the correlation of GSDMB with immune infiltrates and its prognostic role in ccRCC. The transcriptional expression profiles of GSDMB in ccRCC tissues in addition to normal tissues were retrieved from The Cancer Genome Atlas (TCGA) and additionally verified in a different independent cohort, which was obtained from the Gene Expression Omnibus (GEO) database. The Human Protein Atlas and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) were used to assess the protein expression of GSDMB. To assess the effectiveness of GSDMB in distinguishing ccRCC from normal samples, the receiver operating characteristic (ROC) curve analysis was performed. Relationships between GSDMB expression, clinicopathological variables, and overall survival (OS) were evaluated with multivariate methods as well as Kaplan-Meier survival curves. Protein-protein interaction (PPI) networks were created with STRING. Functional enrichment analyses were conducted by utilizing the "ClusterProfiler" package. The Tumor Immune Estimation Resource (TIMER) and tumor-immune system interaction database (TISIDB) were utilized to determine the association between the mRNA expression of GSDMB and immune infiltrates. GSDMB expression was significantly more upregulated in ccRCC tissues compared to surrounding normal tissues. An increase in the mRNA expression of GSDMB was related to the high pathologic stage and advanced TNM stage. The analysis of the ROC curve indicated that GSDMB had an AUC value of 0.820 to distinguish between ccRCC tissues and adjacent normal controls. Kaplan-Meier survival analysis indicated that ccRCC patients with high GSDMB had a poorer prognosis compared to those with low GSDMB ( < 0.001). Correlation analysis showed that the mRNA expression of GSDMB was associated with immune infiltrates and the purity of the tumor. Upregulation of GSDMB is significantly related to immune infiltrates and poor survival in ccRCC. The results of this study indicate that GSDMB could be regarded as a biomarker for the detection of poor prognosis and potential target of immune treatment in ccRCC.
Gasdermin B (GSDMB) 是 gasdermin (GSDM) 家族的一员,它们通过分子中不同的结构域相互作用方式来调节其形成孔和结合脂质的作用。GSDM 家族在细胞分化和增殖的调节中发挥作用,特别是在细胞焦亡过程中。然而,GSDMB 与免疫浸润的相关性及其在透明细胞肾细胞癌(ccRCC)中的预后价值仍未确定。因此,我们评估了 GSDMB 与免疫浸润的相关性及其在 ccRCC 中的预后作用。从癌症基因组图谱(TCGA)中检索到 GSDMB 在 ccRCC 组织中的转录表达谱,并在基因表达综合数据库(GEO)数据库中获得的不同独立队列中进行了进一步验证。人类蛋白质图谱和临床蛋白质组肿瘤分析联盟(CPTAC)用于评估 GSDMB 的蛋白质表达。为了评估 GSDMB 区分 ccRCC 与正常样本的有效性,进行了接收者操作特征(ROC)曲线分析。使用多元方法和 Kaplan-Meier 生存曲线评估 GSDMB 表达与临床病理变量和总生存期(OS)之间的关系。使用 STRING 创建蛋白质-蛋白质相互作用(PPI)网络。利用“ClusterProfiler”软件包进行功能富集分析。使用肿瘤免疫估计资源(TIMER)和肿瘤-免疫系统相互作用数据库(TISIDB)确定 GSDMB mRNA 表达与免疫浸润之间的关系。与周围正常组织相比,ccRCC 组织中 GSDMB 的表达明显上调。GSDMB mRNA 表达的增加与高病理分期和晚期 TNM 分期有关。ROC 曲线分析表明,GSDMB 区分 ccRCC 组织和相邻正常对照的 AUC 值为 0.820。Kaplan-Meier 生存分析表明,GSDMB 高表达的 ccRCC 患者的预后比 GSDMB 低表达的患者差(<0.001)。相关性分析表明,GSDMB 的 mRNA 表达与免疫浸润和肿瘤纯度有关。GSDMB 的上调与 ccRCC 中的免疫浸润和不良预后显著相关。本研究结果表明,GSDMB 可能被视为检测 ccRCC 预后不良和潜在免疫治疗靶点的生物标志物。